Synthesis and reactions of dipyrromethane-2,10-dicarboxylates

Article abstract of DOI:10.1016/S0040-4039(02)00089-8

Dipyrromethane-2,10-dicarboxylates have been prepared. While oxidation and subsequent reaction of 5b with BF₃·OEt₂ yields the corresponding complex 10, ring-closing metathesis of 5d using (NHC)(PCy₃)(Cl)₂Ru=CHPh 7 results in the novel hybrid macrocycle 8. The structure of 10 has been unequivocally established by an X-ray crystallographic study.

Full text of DOI:10.1016/S0040-4039(02)00089-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 1751–1753
Synthesis and reactions of dipyrromethane-2,10-dicarboxylates
Antonio Garrido Montalban,* Antonio J. Herrera, Jes Johannsen, Josephine Beck, Thomas Godet,
Marianna Vrettou, Andrew J. P. White and David J. Williams
Department of Chemistry, Imperial College of Science, Technology and Medicine, South Kensington, London SW7 2AY, UK
Received 12 November 2001; revised 27 December 2001; accepted 11 January 2002
Abstract—Dipyrromethane-2,10-dicarboxylates have been prepared. While oxidation and subsequent reaction of 5b with
BF3·OEt2 yields the corresponding complex 10, ring-closing metathesis of 5d using (NHC)(PCy3)(Cl)2RuꢀCHPh 7 results in the
novel hybrid macrocycle 8. The structure of 10 has been unequivocally established by an X-ray crystallographic study. © 2002
Elsevier Science Ltd. All rights reserved.
Dipyrromethanes, important precursors to porphyrins,1
related polypyrrolic macrocycles2 and pigments,3 can be
oxidatively converted into dipyrromethenes. The latter
are fully conjugated flat bipyrrolic moieties and as such
are useful ligands for chelation to transition metals.4 As
a result, appropriately 2,10-disubstituted analogs may
serve as versatile building blocks for the construction of
novel hybrid macrocycles and complexes derived there-
from. However, to the best of our knowledge, such
studies have not so far been carried out. Herein, we
report our initial investigations towards the elaboration
of new macrocyclic structures and coordination com-
amine proceeded smoothly to give isocyanates 3d,e in
57 and 63% overall yields (Scheme 1). Subsequent
treatment of 3d,e with 3-acetoxy-4-nitrohexane6a in the
presence of 2 equiv. of 1,8-diazabicyclo[5.4.0]undec-7-
ene (DBU) in tetrahydrofuran/isopropanol (1.6:1) gave
pyrroles 4d,e in 68 and 95% yield, respectively. Alterna-
tively, transesterification of 4b with 2 equiv. of the
sodium alkoxide derived from 1e in refluxing tetra-
hydrofuran gave pyrrole ester 4e in an unoptimised
60% yield. This latter procedure could prove useful for
the synthesis of otherwise inaccessible pyrrole-2-car-
boxylates (Scheme 1).
pounds
derived
from
dipyrromethane-2,10-
dicarboxylates.
With the requisite 5-unsubstituted pyrrole-2-carboxy-
lates in hand, the synthesis of the novel dipyrromethane
derivatives 5a–d was undertaken. Compounds 5a,b were
best obtained via treatment of 4a,b with p-nitrobenz-
aldehyde (2:1 molar ratio) in dichloromethane in the
presence of boron trifluoride diethyl etherate
(BF3·OEt2, 0.5 equiv.) (Scheme 1). On the other hand,
the more acid sensitive precursor 4c decomposed upon
exposure to BF3·OEt2. However, clean conversion to
the desired dipyrromethane 5c was achieved with cata-
lytic amounts of PTSA (0.1 equiv.). Similarly, p-tolue-
nesulfonic acid catalysed condensation of pyrrole ester
4d and p-nitrobenzaldehyde (2:1 molar ratio) in
dichloromethane gave the requisite dipyrromethane 5d
in high yield (94%). Interestingly, the same transesterifi-
cation conditions as before (vide supra) resulted mainly
in decomposition of 5b with only small quantities of the
expected dipyrromethane 5e being formed. A similar
result was obtained when bipyrrole 5c and alcohol 1e
were subjected to acidic conditions. However, reaction
of bipyrrole 5b with a stoichiometric amount of alco-
hol 1e in the presence of diphenylammonium triflate8
We decided to begin our studies with meso-aryl-
dipyrromethanes since they can be readily prepared
through the acid catalysed condensation of arylalde-
hydes and pyrroles.5
A series of 5-unsubstituted
pyrrole-2-carboxylates were therefore synthesised.
While compounds 4a–c were obtained according to
published procedures,6 the synthesis of the two new
pyrrole derivatives 4d,e was accomplished through a
similar adaptation of the Barton–Zard protocol.7 Thus,
esterification of glycine with 2 equiv. of each of the
alcohols 1d,e and p-toluenesulfonic acid (PTSA) gave
the corresponding esters 2d,e as the p-toluenesulfonate
salts in 84 and 95% yield, respectively. N-Formylglyci-
nate formation using methyl formate and triethylamine
and dehydration with phosphoryl chloride–triethyl-
Keywords: dipyrromethanes; dipyrromethenes; ring-closing metathe-
sis; macrocycles; complexes.
* Corresponding author: Tel.: 0207 594 5764; fax: 0207 594 5805;
e-mail: agmont@ic.ac.uk
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00089-8

1752
A. Garrido Montalban et al. / Tetrahedron Letters 43 (2002) 1751–1753
1. HCO2Me, Et3N
reflux, 16 h
O
PTSA
RO
RO
NH3 p-TsO-
NC
NH2
ROH
HO
O
toluene
reflux, 14 h
O
2. POCl3/Et3N
CH2Cl2, 0 oC, 1 h
1d,e
2d (84%), e (95%)
3d (57%), e (63%)
OAc
DBU
a R = Bn
Et
b R = Et
c R = tBu
THF/iPrOH
Et
NO2
rt, 6 h
NO2
NO2
d R = (CH2)3CH=CH2
e R = (CH2)4CH=CH2
Et
Et
Et
Et
O
NO2
Et
CH2Cl2
acid, rt
14 h
Et
RO2C
RO2C
NH HN
N
H
CO2R
Et
Et
4a6a
b6b
c6c
5a (85%)
Et
Na, 1e
THF
reflux, 4 h
60%
Et
H2C=HC(H2C)4O2C
b (65%)
c (94%)
d (94%)
e (60%)
NH HN
DPAT, TMSCl
1e, toluene, 80 oC
d (68%)
e (95%)
CO2Et
14 h
6
Scheme 1.
(DPAT, 10 mol%) and chlorotrimethylsilane (TMSCl,
10 mol%) in toluene gave the desired product 5e
(60%) along with the mixed diester 6.
In parallel, oxidation of 5a,b to their corresponding
dipyrromethene derivatives 9a,b occurred readily with
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in
dichloromethane (Scheme 3). Subsequent treatment of
9b with an excess of BF3·OEt2 in toluene in the pres-
ence of triethylamine at ambient temperature gave the
corresponding boron complex 10 in high yield (95%).
The solid state structure of 10 is illustrated in Fig.
1.11 The two pyrrole rings and their linking carbon
As the next step, the ring-closing metathesis of
bisalkene 5d was examined. Thus, a solution (0.01 M)
of 5d in dichloromethane was treated with 5 mol% of
(NHC)(PCy3)(Cl)2RuꢀCHPh 79 (Scheme 2). After
fourteen hours at ambient temperature the formation
of a new less polar material could be detected along
with what was initially believed to be the starting
material. However, no change in composition
occurred upon the addition of a further 5 mol% of
Grubb’s catalyst 7. Fortuitously, proton and carbon
NMR analysis of the product revealed it to consist
only of a cis/trans-mixture of the desired macrocycle
8.10 In addition, high-resolution mass ion measure-
ment and all other spectroscopic data were consistent
with the proposed structures.
,
atom are co-planar to within 0.09 A, the boron atom
,
lying 0.18 A out of this plane. Thus, the central
C3N2B ring has a slightly folded conformation, there
being a ca. 8° fold about the N···N vector (the C3N2
,
portion being planar to within 0.008 A), and this
results in a pseudo axial/equatorial disposition of the
two fluorine substituents. The para-nitrophenyl unit is
oriented orthogonally (88°) to the plane of the central
six-membered heterocyclic ring.
NO2
This work clearly illustrates that dipyrromethane-2,10-
dicarboxylates are indeed useful molecular platforms
for the potential development of novel hybrid macro-
cycles and complexes derived thereof. Further aspects
of the chemistry of such systems will be reported in
due course.
N Ms
Ph
Ru
Ms
Cl
Cl
N
Et
Et
PCy3
Et
Et
7
NH HN
5d
O
O
CH2Cl2, rt, 14 h
O
O
Acknowledgements
We thank Professor A. G. M. Barrett, the ERAS-
MUS Scheme (J.J., J.B. and T.G.) and the Spanish
Government (A.J.H.) for generous support of our
studies.
8 (98%)
Scheme 2.

A. Garrido Montalban et al. / Tetrahedron Letters 43 (2002) 1751–1753
1753
NO2
NO2
Et
Et
Et
Et
BF3.OEt2
DDQ
5a,b
toluene
Et3N, rt
30 min
CH2Cl2
rt, 16 h
Et
CO2Et
Et
CO2R
9a (57%), b (90%)
Et
EtO2C
Et
N
B
N
NH
N
RO2C
F
F
10 (95%)
Scheme 3.
5. (a) Bru¨ckner, C.; Sternberg, E. D.; Boyle, R. W.; Dol-
phin, D. Chem. Commun. 1997, 1689 and references cited
therein; (b) Lee, C.-H.; Lindsey, J. S. Tetrahedron 1994,
50, 11427.
6. (a) Lash, T. D.; Belletini, J. R.; Bastian, J. A.; Couch, K.
B. Synthesis 1994, 170; (b) Sessler, J. L.; Mozaffari, A.;
Johnson, M. R. Org. Synth. 1992, 70, 68; (c) Barton, D.
H. R.; Kervagoret, J.; Zard, S. Z. Tetrahedron 1990, 46,
7587.
7. Barton, D. H. R.; Zard, S. Z. J. Chem. Soc., Chem.
Commun. 1985, 1098.
8. Wakasugi, K.; Misaki, T.; Yamada, K.; Tanabe, Y.
Tetrahedron Lett. 2000, 41, 5249.
9. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org.
Lett. 1999, 1, 953.
10. Selected data for 8: 1H NMR (300 MHz, CDCl3): l
0.95–1.05 (m, 6H), 1.14–1.25 (m, 6H), 1.64–1.74 (m, 4H),
2.06–2.15 (m, 4H), 2.34–2.44 (m, 4H), 2.75–2.85 (m, 4H),
4.24 (t, J=5.2 Hz, 4H, OCH2), 5.38 (t, J=4.8 Hz, 2H,
CHꢀCH), 5.67 and 5.70 (two singlets in the ratio 1:2.3,
respectively, 1H, ArCH), 7.25 (d, J=8.6 Hz, 2H), 8.17
and 8.18 (two doublets in the ratio 2.3:1, respectively,
J=8.6 Hz, 2H, Ar), 8.23 (br s, 2H). HRMS (FAB) calcd
+
’
+
’
for C33H41N3O6: (M ) 575.2995; found: (M ) 575.3020.
Figure 1. X-Ray crystal structure of 10.
11. Crystal data for 10: C29H34BF2N3O6, M=569.4, mono-
clinic, P21/c (no. 14), a=20.478(3), b=17.580(2), c=
3
,
,
8.131(3) A, i=100.99(2)°, V=2873(1) A , Z=4,
D
calcd=1.316 g cm−3, v(Cu Ka)=8.37 cm−1, T=193 K,
References
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